Blacks are disproportionately affected by kidney disease, exhibiting high rates of age-adjusted incident CKD (glomerular filtration rate [GFR] <60 ml/min/1.73 m2) and more rapid progression to end-stage renal disease and cardiovascular disease. Prior studies in this area have been limited by the use of creatinine-based measures of kidney function that may mask early kidney disease (declines in kidney function at GFR e 60 ml/min/1.73 m2) and by the absence of longitudinal data on cohorts with adequate numbers of Black participants and no prevalent disease at baseline. We propose to combine repeated measurements of cystatin C, a marker of kidney function, with longitudinal data on risk factor and cardiovascular disease development in the NHLBI-funded Coronary Artery Risk Development in Young Adults (CARDIA) cohort. Cystatin C may offer advantages over creatinine-based estimates of kidney function for detecting early declines in function. CARDIA offers a cohort of 5115 young adults with similar numbers of Blacks and Whites and of men and women, who at baseline were aged 18-30 and free of cardiovascular disease. After 20 years of follow-up, Black CARDIA participants (compared with Whites) have 2-fold higher rates of hypertension, 4-fold higher rates of kidney dysfunction, and 10-fold higher rates of heart failure, making this cohort ideal for exploring factors that place Blacks at particular risk for these processes. We will: (1) evaluate declines in kidney function, hypothesizing (a) a greater decline in Blacks that is mediated by hypertension, socioeconomic factors, and inflammation, and (b) that cystatin C will be more sensitive than creatinine-based estimates for detecting declines in kidney function at GFR = 60 ml/min/1.73 m2; (2) determine the association between declining kidney function and subsequent sub-clinical cardiovascular disease, hypothesizing (a) that cystatin C will be a stronger predictor than creatinine-based estimates of GFR or microalbuminuria, and (b) that cystatin C will predict carotid wall thickness more strongly in Blacks, but will predict coronary artery calcium more strongly in Whites; (3) determine the association between declining kidney function and subsequent cardiovascular disease, hypothesizing that cystatin C will be a better predictor of cardiovascular risk than creatinine-based estimates of kidney function. The results of this epidemiologic study will provide important insights into the timing of CKD development in young to middle-aged people and the relative importance of various risk factors in kidney function decline and cardiovascular risk. These findings will be important as a guide for preventive efforts and future research, particularly in Blacks. [unreadable] [unreadable] [unreadable]